Mr. Hong-Toan Lai

About Mr. Hong-Toan Lai

As a final-year PhD candidate at Paris-Saclay University and the Gustave Roussy Cancer Campus, with an anticipated defense in December 2025, Hong-Toan Lai explores the crucial communication between mitochondria and the nucleus and its role in driving tumor aggressiveness. His groundbreaking research has led to the discovery of a first-in-class flavonoid that disrupts the AIF/CHCHD4 complex, a critical mediator of nucleus-encoded protein import into mitochondria, offering a novel therapeutic strategy for pediatric osteosarcoma. This work has resulted in a pending patent and the launch of a deep-tech spin-off project. Additionally, Hong-Toan has developed an innovative concept of targetable metabolic vulnerabilities, paving the way for synergistic anti-cancer therapeutic combinations.
Supported by prestigious fellowships, including Fondation pour la Recherche Médicale, Germaine de Staël, and Taxe d’Apprentissage, Hong-Toan integrates rigorous wet-lab experimentation with advanced RNA-seq, metabolomics, and machine-learning pipelines to uncover therapeutically exploitable metabolic reprogramming in cancer.

Meet Mr. Lai

Research Expertise

Hong-Toan’s skill set combines mitochondrial biology, cancer metabolism, and drug discovery, with cutting-edge techniques with translational innovation:

• Molecular and Cellular Biology: Co-immunoprecipitation (co-IP), (RT-q)PCR, Immunofluorescence, Confocal Microscopy, Clonogenic/proliferation assays (MTT, LDH),…

• Mitochondrial Bioenergetics: Seahorse XF flux analysis and structural-functional studies of the AIF/CHCHD4 complex to assess mitochondrial function and dynamics.

• Multi-Omics Profiling: Experienced in RNA-seq analysis (DESeq2, GO, GSEA) and untargeted metabolomics (KEGG, MetaboAnalyst) to map cancer-specific metabolic rewiring.

• Genome Engineering and In Vivo Models: CRISPR/Cas9-based knockout and knock-in cell line development, as well as orthotopic xenograft models in mice with tumor bioluminescence imaging.

• Translational Drug Discovery: Expertise in hit-to-lead optimization of bioactive flavonoids, collaborating with chemists and clinicians to advance therapeutic pipelines.

Research and Publications

Patent & Publications

Patent

• Brenner C*, Duong TH, Figadère B, Gaspar N, Geoerger B, Lai HT, Marchais A, Pedroso D. M-030-E05, a molecule targeting AIF/CHCHD4 complex for anticancer treatment. Patent GR, CNRS, INSERM, submitted. *Alphabetical order.

Publications

• Lai HT, Nguyen TNA, Pedroso D, Fernandes R, Vassetzky Y, Marchais A, Gaspar N, Duong TH, Geoerger B, Brenner C. Combined targeting of AIF/CHCHD4 interaction and GLS1 exploits metabolic vulnerabilities in pediatric osteosarcoma. In preparation.

• Lai HT, Pedroso D, Da Costa Marques J, Fernandes R, Nguyen TNA et al. Engineered flavonoid disrupts mitochondrial AIF/CHCHD4 complex for targeted cancer therapy. bioRxiv; Acta Pharmaceutica Sinica B (in revision) (IF = 14.6). doi: 10.1101/2025.03.13.642976.

• Nguyen TNA, Lai HT, Fernandes R et al. Apoptosis-Inducing Factor (AIF) at the crossroad of cell survival and cell death: implications for cancer and mitochondrial diseases. Cell Communication and Signaling 23, 264 (2025) (IF = 8.9). doi: 10.1186/s12964-025-02272-2.

• Lai HT, Naumova N, Marchais A et al. Insight into the interplay between mitochondria-regulated cell death and energetic metabolism in osteosarcoma. Front Cell Dev Biol 10:948097 (2022) (IF = 4.3). doi: 10.3389/fcell.2022.948097.

• Lai HT, Canoy RJ, Campanella M et al. Ca²⁺ transportome and inter-organelle communication in hepatocellular carcinoma. Cells 11(5):815 (2022) (IF = 5.2). doi: 10.3390/cells11050815.

• Liu D, Lai HT, Peyre F, Brenner C. Multiple analysis of mitochondrial metabolism, autophagy and cell death. Methods Cell Biol 164:95-112 (2021) (IF = 1.4). doi: 10.1016/bs.mcb.2021.02.001.

Research

• 02/2022 - 06 / 2026 
  Co-founder, Scientific Advisor | METSY Therapeutics, Gustave Roussy Institute, Villejuif, France
 
  Spearheading a spin-off startup developing chemically-modified flavonoids for anti-cancer therapy, following the patent of a flavonoid targeting AIF/CHCHD4
  
  

• 12 / 2021 – 07 / 2021 
  Lab Technician | CNRS UMR9018 METSY, Gustave Roussy Institute
 
  Project “Metabolic characterization of osteosarcoma cell lines” – Supervisors Dr Catherine Brenner, Dr Birgit Geoerger
  
  

• 06 / 2021 – 01 / 2021 
  Master 2 Internship | CNRS UMR9018 METSY, Gustave Roussy Institute
 
  Project “Role of mitochondrial calcium & MICU1 as regulators of metabolism and gene expression in cancer” – Supervisors Dr Catherine Brenner, Dr Yegor Vassetzky
  

• 05 / 2020 – 03 / 2020 
  Master 1 Internship | CNRS UMR9018 METSY
 Project “Evaluation of the metabolic and cytotoxic activity of compounds interrupting the CHCHD4–AIF interaction” – Supervisors Dr Catherine Brenner, Dr Dawei Liu
  
  

• 07 / 2019 – 06 / 2019 
  Bachelor’s Internship | BETA INNOV, IRBM, CHRU Montpellier
 
  Project “Evaluation of the efficacy of BIM2b inducing cell death in glioblastoma astrocytes” – Supervisors Dr Marcel Mersel, Dr Clovis Rakotoarivelo
  
  

• 2017 - 2018 
  Bachelor’s Internship | INSERM U1183, Faculty of Medicine Montpellier, France

  Two-year project “Study of the functionality of T-regulatory lymphocytes in the pathophysiology of Rheumatoid Purpura in children” – Supervisor Prof Tu-Anh Tran